20-50535747-A-G

Variant names:

• chr20-50535747-A-G
• rs2426158
• NM_002827.4:c.63+25157A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.63+25157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,106 control chromosomes in the GnomAD database, including 4,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4597 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 7 publications found

Genes affected

PTPN1 (HGNC:9642): (protein tyrosine phosphatase non-receptor type 1) The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

PTPN1 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	NM_002827.4	MANE Select	c.63+25157A>G		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.-66+25157A>G		intron	N/A	NP_001265547.1	B4DSN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	ENST00000371621.5	TSL:1 MANE Select	c.63+25157A>G		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.63+25157A>G		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.63+25157A>G		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37006 AN: 151988 Hom.: 4587 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 37032 AN: 152106 Hom.: 4597 Cov.: 32 AF XY: 0.239 AC XY: 17801 AN XY: 74340

African (AFR) AF: 0.204 AC: 8479 AN: 41480

American (AMR) AF: 0.320 AC: 4886 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 997 AN: 3468

East Asian (EAS) AF: 0.0948 AC: 491 AN: 5182

South Asian (SAS) AF: 0.133 AC: 641 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2488 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18271 AN: 67990

Other (OTH) AF: 0.251 AC: 530 AN: 2112

Alfa AF: 0.177 Hom.: 471

Bravo AF: 0.252

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		-0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2426158; hg19: chr20-49152284;